17-hydroxyprogesterone ester-containing oral compositions and related methods

Abstract

The present invention provides for bioavailable oral dosage forms containing esters of 17-hydroxyprogesterone as well as related methods. The oral dosage forms can be formulated for pregnancy support and can include a therapeutically effective amount of an ester of 17-hydroxyprogesterone and a pharmaceutically acceptable carrier. In another embodiment, a pharmaceutically acceptable oral dosage form for pregnancy support is provided. The pharmaceutically acceptable oral dosage can include a therapeutically effective amount of an ester of 17-hydroxyprogesterone and a pharmaceutically acceptable carrier. The oral dosage form can, when measured using a USP Type-II dissolution apparatus in 900 mL of deionized water with 0.5 (w/v) of sodium lauryl sulfate at 50 RPM at 37° C., release at least 20 wt % of the dose of the ester of 17-hydroxyprogesterone after 60 minutes, or in the alternative release at least 20 wt % more after 60 minutes than an equivalently dosed oral dosage form without the carrier.

What is claimed is: 
     
       1. A method of treating a pregnant female at risk of having a preterm birth, said method comprising administering to a pregnant female having one or more serum biomarkers that indicate said pregnant female is at risk of preterm birth a pharmaceutical composition comprising a therapeutically effective amount of 17-hydroxyprogesterone caproate and a pharmaceutically acceptable carrier comprising a lipophilic additive selected from benzyl benzoate, castor oil and mixtures thereof, said lipophilic additive comprising at least 50 weight/weight percent (w/w %) of the carrier and said pharmaceutical composition having 50 w/w % or less castor oil and 50 w/w % or less benzyl benzoate wherein said pharmaceutical composition is prepared by combining castor oil, benzyl benzoate and 17-hydroxyprogesterone caproate with the proviso that benzyl alcohol is not combined with the pharmaceutical composition. 
     
     
       2. A method of treating a pregnant female at risk of having a preterm birth, said method comprising administration to a pregnant female having one or more serum biomarkers that indicate said pregnant female is at risk of preterm birth a pharmaceutical composition having a therapeutically effective amount of 17-hydroxyprogesterone caproate and a pharmaceutically acceptable carrier comprising a lipophilic additive selected from benzyl benzoate, castor oil and mixtures thereof, said lipophilic additive comprising at least 50 weight/weight percent (w/w %) of the carrier and said pharmaceutical composition having 50 w/w % or less castor oil and 50 w/w % or less benzyl benzoate wherein said pharmaceutical composition when measured using a USP Type-II dissolution apparatus in 900 mL of simulated intestinal fluid having 0.5 w/w % sodium lauryl sulfate at 50 RPM at 37° C., releases at least 20% of the 17-hydroxyprogesterone caproate at 60 minutes with the proviso that the composition does not include benzyl alcohol. 
     
     
       3. The method of  claim 2 , wherein said pharmaceutical composition is in a capsule. 
     
     
       4. The method of  claim 2 , wherein said pharmaceutical composition is formulated as a tablet. 
     
     
       5. The method of  claim 3 , wherein said capsule includes from about 30 mg to about 300 mg of 17-hydroxyprogesterone caproate. 
     
     
       6. The method of  claim 4 , wherein said tablet includes from about 20 mg to about 800 mg of 17-hydroxyprogesterone caproate. 
     
     
       7. The method of  claim 2 , wherein said pharmaceutical composition is a controlled release dosage form. 
     
     
       8. The method of  claim 2 , wherein the pharmaceutical composition has from about 28 to about 48 w/w % benzyl benzoate. 
     
     
       9. The method of  claim 2 , wherein the pharmaceutical composition has from about 23 to about 25 w/w % castor oil. 
     
     
       10. The method of  claim 2 , wherein the pharmaceutical composition has about 5 to about 30 w/w 17-hydroxyprogesterone caproate. 
     
     
       11. The method of  claim 2 , wherein the pharmaceutical composition has about 25% w/w % 17-hydroxyprogesterone caproate. 
     
     
       12. The method of  claim 2 , wherein the pharmaceutical composition has the 17-hydroxyprogesterone caproate in a fully solubilized form.